Angiotensin II (Ang II) is an important peptide of the renin-angiotensin system (RAS) that is important in regulating fluid balance, sodium intake, thirst and blood pressure. The RAS is highly activated in inflammatory diseases such as shock and encephalitis. An important characteristic of central nervous system inflammatory disease is an increase in the growth and proliferation of astrocytes, a condition known as reactive astrocytosis. Reactive astrocytosis is known to alter the blood brain barrier and to inhibit axonal regeneration. Studies that elucidate the mechanisms involved in astrocyte growth and proliferation will be important in providing treatment strategies for inflammatory disease states of the central nervous system. I hypothesize that Ang II plays a role in astrocyte growth and proliferation and thus in reactive astrocytosis. In previous studies, the P.I. and colleagues have found that Ang II stimulates the astrocyte growth by activating mitogen-activated protein kinases through an effect on tyrosine kinases. The P.I. is requesting funding to determine the mechanisms by which Ang II controls astrocyte growth and proliferation. Specifically, I will investigate: a) which of the tyrosine kinases is involved in Ang II-mediated astrocyte growth and proliferation; b) the role of the intracellular signaling molecules phosphoinositide 3-kinase and p90 KDa ribosomal s6 kinase in Ang II-mediated astrocyte growth and proliferation; and c) the transcription factors involved in Ang II-mediated astrocyte growth and proliferation. The P.I. is experienced in preparing primary cultures of astrocytes, in running gel electrophoresis and performing other experimental techniques necessary to complete the project. The results of the studies will be submitted for publication in peer reviewed journals (Hypertension or Glia) and presented at National Scientific Meetings (such as Experimental Biology). The P.I. will also apply for a National Institute of Health grant or an American Heart Association grant using data garnered from this proposal.